An abnormal increase in blood uric acid level, i.e., hyperuricemia, is a disorder that has close relation to gout, renal dysfunction, urolithiasis, etc. (Diagnosis and Treatment, 220-224, 244-248 (2002)). It is known that, in organ transplantation (Ren. Fail., 361-7 (2002)) or chemotherapy for cancer (Am. J. Health Syst. Pharm., 2213-22 (2003)), serum uric acid levels increase significantly, thereby causing renal dysfunction, or in the case of chemotherapy, serum uric acid levels increase significantly due to the rapid amount of cellular destruction (tumor lysis syndrome).
Hyperuricemia is a condition or disorder that precedes gout, resulting from increased production or decreased excretion of uric acid, or from a combination of the two processes. In an individual with hyperuricemia, plasma and extracellular fluids are supersaturated with urate, and crystal deposition in tissue is likely to occur, resulting in the clinical manifestations of gout. When crystals form in the joints it causes recurring attacks of joint inflammation. Chronic gout can also lead to deposits of hard lumps of uric acid in and around the joints and may cause joint destruction and decreased kidney function.
An agent for treating hyperuricemia may be roughly classified into an uricosuric agent or an uric acid synthesis inhibitor. The uricosuric agent may be ineffective for cases whose renal function has lowered, and therefore allopurinol, an uric acid synthesis inhibitor, is suitably used for patients having a lowered renal function.
Xanthine oxidase is an enzyme that controls the biosynthesis of uric acid, and use of a xanthine oxidase inhibitor to inhibit this enzyme is an effective treatment of hyperuricemia and various diseases caused thereby, as an uric acid synthesis inhibitor. Allopurinol is the only xanthine oxidase inhibitor that has been put into practical use at present for clinical treatment, though it is known to induce undesirable side effects.